Zhuhai Fudan Innovation Research Institute

Heavy monsoon rainfall ravaged a large swath of East Asia in summer 2020. Severe flooding of the Yangtze River displaced millions of residents in the midst of a historic public health crisis. This extreme rainy season was not anticipated from El Niño conditions. Using observations and model experiments, we show that the record strong Indian Ocean Dipole event in 2019 is an important contributor to the extreme Yangtze flooding of 2020. This Indian Ocean mode and a weak El Niño in the Pacific excite downwelling oceanic Rossby waves that propagate slowly westward south of the equator. At a mooring in the Southwest Indian Ocean, the thermocline deepens by a record 70 m in late 2019. The deepened thermocline helps sustain the Indian Ocean warming through the 2020 summer. The Indian Ocean warming forces an anomalous anticyclone in the lower troposphere over the Indo-Northwest Pacific region and intensifies the upper-level westerly jet over East Asia, leading to heavy summer rainfall in the Yangtze Basin. These coupled ocean-atmosphere processes beyond the equatorial Pacific provide predictability. Indeed, dynamic models initialized with observed ocean state predicted the heavy summer rainfall in the Yangtze Basin as early as April 2020.

Abstract The photocatalytic properties of TiO 2 have aroused a broad range of research interest since 1972 due to its abundance, chemical stability, and easily available nature. To increase its overall activity, in the past few decades, much effort has been devoted to the fabrication of advanced TiO 2 ‐based photocatalysts with visible‐light response and these photocatalysts have shown great potential in the field of solar energy utilization. Here, recent progress in the investigation of visible‐light responsive TiO 2 ‐based materials are reviewed. Notably, the fabrication strategies and corresponding chemical/physical properties of visible‐light responsive TiO 2 ‐based materials are described in detail, with a focus on bandgap engineering and junction engineering from the perspective of light absorption, charge transfer and separation, and surface reactions. Their applications in solar‐fuel production, organic synthesis, bacterial disinfection, pollutant degradation and nitrogen fixation are also discussed. Moreover, the new trends and ongoing challenges in this field are proposed and highlighted.

Ultrafast artificial skin enables unprecedented tactile internet applications in prosthetics, robotics, and human-machine interactions. However, current artificial skin systems that rely on front-end interface electronics typically perform redundant data transfer and analogue-to-digital conversions for decision-making, causing long latency (milliseconds). Here, a near-sensor analogue computing system based on a flexible memristor array for artificial skin applications is reported. This system, which seamlessly integrates a tactile sensor array with a flexible hafnium oxide memristor array, can simultaneously sense and compute raw multiple analogue pressure signals without interface electronics. As a proof-of-concept, the system is used for real-time noise reduction and edge detection of tactile stimuli. One sensing-computing operation of this system takes about 400 ns and consumes on average 1000 times less power than a conventional interface electronic system. The results demonstrate that near-sensor analogue computing offers an ultrafast and energy-efficient route to large-scale artificial skin systems.

In the post-Moore era, advanced packaging is becoming more critical to meet the everlasting demands of electronic products with smaller size, more powerful performance and lower cost. In this paper, developments in advanced packaging have been discussed, such as 3D IC packaging, fan-out packaging, and chiplet packaging. Insights on the major advantages and challenges have also been briefly introduced. Our prospects about the solutions to some fundamental issues in sustainable development of advanced packaging have also been elucidated. The critical aspects and opportunities lie in standardization, co-design tools, new handling technologies, as well as multi-scale modeling and simulation.

Abstract The Arctic has experienced a warming rate higher than the global mean in the past decades, but previous studies show that there are large uncertainties associated with future Arctic temperature projections. In this study, near-surface mean temperatures in the Arctic are analyzed from 22 models participating in phase 6 of the Coupled Model Intercomparison Project (CMIP6). Compared with the ERA5 reanalysis, most CMIP6 models underestimate the observed mean temperature in the Arctic during 1979–2014. The largest cold biases are found over the Greenland Sea the Barents Sea, and the Kara Sea. Under the SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios, the multimodel ensemble mean of 22 CMIP6 models exhibits significant Arctic warming in the future and the warming rate is more than twice that of the global/Northern Hemisphere mean. Model spread is the largest contributor to the overall uncertainty in projections, which accounts for 55.4% of the total uncertainty at the start of projections in 2015 and remains at 32.9% at the end of projections in 2095. Internal variability uncertainty accounts for 39.3% of the total uncertainty at the start of projections but decreases to 6.5% at the end of the twenty-first century, while scenario uncertainty rapidly increases from 5.3% to 60.7% over the period from 2015 to 2095. It is found that the largest model uncertainties are consistent cold bias in the oceanic regions in the models, which is connected with excessive sea ice area caused by the weak Atlantic poleward heat transport. These results suggest that large intermodel spread and uncertainties exist in the CMIP6 models’ simulation and projection of the Arctic near-surface temperature and that there are different responses over the ocean and land in the Arctic to greenhouse gas forcing. Future research needs to pay more attention to the different characteristics and mechanisms of Arctic Ocean and land warming to reduce the spread.

Abstract Climate change is expected to result in more frequent and intense heat waves (HWs) in South Asia (SA). The simultaneous increases in temperature and population will exacerbate the population exposure to future HWs. Here we estimate the future population exposure to daytime and nighttime HWs in SA using the Coupled Model Intercomparison Project 6 (CMIP6) models under four Shared Socioeconomic Pathways (SSPs) during 2061–2100, relative to 1975–2014. The results show that the projected frequency and spatial extent of the daytime (nighttime) HWs will be higher under scenario SSP5‐8.5, followed by SSP2‐4.5, SSP3‐7.0, and SSP1‐2.6 (SSP5‐8.5, followed by SSP3‐7.0, SSP2‐4.5, and SSP1‐2.6), relative to the historical period. The approach presented here allows decomposing the effects of climate change and future population on the overall exposure. The results reveal that the compounding effects of projected trends in population and HWs will significantly escalate the population exposure to HWs. Under the selected SSPs, the total population exposure to daytime and nighttime HWs ranges from 185 to 492 and 204–555 million people‐event, respectively, with the maximum exposure occurring in the Indo‐Gigantic Plain. The wide range of exposed populations highlights the sensitivity of the overall exposure to our future socioeconomic pathway decisions, emphasizing the importance of curbing anthropogenic greenhouse gas emissions and adopting sustainable urban planning solutions to minimize the potential socioeconomic and health impacts of HWs.

Abstract Mimicking natural nitrogenase to create highly efficient single‐atom catalysts (SACs) for ambient N 2 fixation is highly desired, but still challenging. Herein, S‐coordinated Fe SACs on mesoporous TiO 2 have been constructed by a lattice‐confined strategy. The extended X‐ray absorption fine structure and X‐ray photoelectron spectroscopy spectra demonstrate that Fe atoms are anchored in TiO 2 lattice via the FeS 2 O 2 coordination configuration. Theoretical calculations reveal that FeS 2 O 2 sites are the active centers for electrocatalytic nitrogen reduction reaction (NRR). Moreover, the finite element analysis shows that confinement of opened and ordered mesopores can facilitate the mass transport and offer an enlarged active surface area for NRR. As a result, this catalyst delivers a favorable NH 3 yield rate of 18.3 μg h −1 mg cat. −1 with a high Faradaic efficiency of 17.3 % at −0.20 V versus a reversible hydrogen electrode. Most importantly, this lattice‐confined strategy is universal and can also be applied to Ni 1 S x @TiO 2 , Co 1 S x @TiO 2 , Mo 1 S x @TiO 2 , and Cu 1 S x @TiO 2 SACs. Our study provides new hints for the design and biomimetic synthesis of highly efficient NRR electrocatalysts.

Over the past few decades, there have been major developments in transition metal-catalyzed asymmetric cyclization reactions, enabling the convenient access to a wide spectrum of structurally diverse chiral carbo- and hetero-cycles, common skeletons found in fine chemicals, natural products, pharmaceuticals, agrochemicals, and materials. In particular, a plethora of enantioselective cyclization reactions have been promoted by chiral palladium catalysts owing to their outstanding features. This review aims to collect the latest advancements in enantioselective palladium-catalyzed cyclization reactions over the past eleven years, and it is organized into thirteen sections depending on the different types of transformations involved.

Twitter has become a major social media platform and has attracted considerable interest among researchers in sentiment analysis. Research into Twitter Sentiment Analysis (TSA) is an active subfield of text mining. TSA refers to the use of computers to process the subjective nature of Twitter data, including its opinions and sentiments. In this research, a thorough review of the most recent developments in this area, and a wide range of newly proposed algorithms and applications are explored. Each publication is arranged into a category based on its significance to a particular type of TSA method. The purpose of this survey is to provide a concise, nearly comprehensive overview of TSA techniques and related fields. The primary contributions of the survey are the detailed classifications of numerous recent articles and the depiction of the current direction of research in the field of TSA.

Abstract The effect of climate change on tropical cyclone intensity has been an important scientific issue for a few decades. Although theory and modeling suggest the intensification of tropical cyclones in a warming climate, there are uncertainties in the assessed and projected responses of tropical cyclone intensity to climate change. While a few comprehensive reviews have already provided an assessment of the effect of climate change on tropical cyclone activity including tropical cyclone intensity, this review focuses mainly on the understanding of the effect of climate change on basin-wide tropical cyclone intensity, including indices for basin-wide tropical cyclone intensity, historical datasets used for intensity trend detection, environmental control of tropical cyclone intensity, detection and simulation of tropical cyclone intensity change, and some issues on the assessment of the effect of climate change on tropical cyclone intensity. In addition to the uncertainty in the historical datasets, intertwined natural variabilities, the considerable model bias in the projected large-scale environment, and poorly simulated inner-core structures of tropical cyclones, it is suggested that factors controlling the basin-wide intensity can be different from individual tropical cyclones since the assessment of the effect of climate change treats tropical cyclones in a basin as a whole.

With economic growth, the demand for power systems is increasingly large. Short-term load forecasting (STLF) becomes an indispensable factor to enhance the application of a smart grid (SG). Other than forecasting aggregated residential loads in a large scale, it is still an urgent problem to improve the accuracy of power load forecasting for individual energy users due to high volatility and uncertainty. However, as an important variable that affects the power consumption pattern, the influence of weather factors on residential load prediction is rarely studied. In this paper, we review the related research of power load forecasting and introduce a short-term residential load forecasting model based on a long short-term memory (LSTM) recurrent neural network with weather features as an input.

Abstract Nitrogen (N2) fixation under mild conditions is a promising approach for green production of ammonia (NH3). In the past decades, various advanced catalysts have been fabricated to achieve this goal through electrocatalytic and photocatalytic processes. Among them, the TiO2‐based catalysts have been recognized as promising candidates due to their high activity, low cost, chemical stability, and nontoxicity. In this review, recent advances in the fabrication of high‐performance TiO2‐based materials for N2 reduction reaction (NRR) under mild conditions are summarized, including electrocatalytic and photocatalytic NRR. The design principles, synthetic strategies, and corresponding chemical/physical properties of TiO2‐based NRR catalysts are described in detail. Moreover, the key challenges and potential opportunities in this field are presented and discussed.

Dear Editor, Previously, the Mendelian phenotypes in human oocyte maturation arrest, fertilization failure and early embryonic arrest, are largely underestimated. In recent years, “missing” Mendelian phenotypes and genes in these processes are beginning to be uncovered by us and others (Huang et al., 2014; Alazami et al., 2015; Feng et al., 2016; Xu et al., 2016; Chen et al., 2017; Sang et al., 2019). However, the genetic basis for majority of patients resulting from abnormalities in these phenotypes remains to be elucidated. The cell division cycle 20 (CDC20, HGNC:1723) is the co-activator of anaphase-promoting complex/cyclosome (APC/C) during mitosis, and plays a role in maintaining the genome by regulating spindle assembly checkpoints (Musacchio and Hardwick, 2002). In oocytes, the activation of APC/C by CDC20 is a key step in homologue disjunction and in transition from meiosis I to meiosis II (Jones, 2011). CDC20 is therefore an essential component of the mammalian cell cycle mechanism regulating both miotic and meiotic exit. Although CDC20 is an extensively studied gene, until now, no solid evidence has been provided to establish the causal relationship between CDC20 mutations and human diseases. The only report was an association study relating CDC20 mutations with idiopathic azoospermia (Li et al., 2017). Here, we identified biallelic CDC20 mutations in five infertile individuals with oocyte maturation arrest, fertilization failure, and early embryonic arrest. We investigated the effects of the corresponding mutations in cell lines and mouse oocytes and explored a potential therapeutic treatment by direct CDC20 cRNA injection. The probands in families 1 and 2 had normal menstrual cycles and had been diagnosed as primary infertility with unknown reasons for several years (Table S1). Both of the probands came from consanguineous families (Fig. 1A). The probands in family 1 had undergone two failed in vitro fertilization (IVF) attempts and one failed intracytoplasmic sperm injection (ICSI). In her ICSI cycle, eleven oocytes were obtained, and ten oocytes were arrested at the germinal vesicle (GV) or metaphase I (MI) stage (Fig. 1B), only one was matured and fertilized, but was arrested at three-cell stage (Table S1). The proband in family 2 had undergone two failed ICSI cycles. All of the retrieved oocytes were arrested at the MI stage (Table S1). In summary, both two probands had phenotypes of oocyte maturation arrest in their ICSI attempts. Whole-exome sequencing and homozygosity mapping was performed (Fig. S1). By a recessive inheritance model, we identified two homozygous missense mutations (c.683A>G, p.Tyr228Cys and c.1316T>G, p.Leu439Arg) in CDC20, respectively (Fig. 1A). Because the parents of both probands were unavailable, in order to rule out the possibility that the homozygous status of CDC20 resulted from the deletion of one allele, we performed a copy number variation (CNV) analysis. There was no CNV for CDC20 in the probands of both families, which confirmed that the mutations in the two individuals were indeed homozygous (Fig. S2A and S2B). Identification of mutations in CDC20 and effects of the mutations on protein level of CDC20 and cyclin B1. (A) Five pedigrees presented with abnormalities in oocyte maturation, fertilization and early embryonic development. Question marks indicate unavailable DNA samples, double lines denote consanguineous marriage, the equal sign denote infertility. (B) The morphology of normal and affected individual oocytes at 0 h, 2 h and 24 h after retrieved. The black arrows indicate the first polar body (PB1), and the white arrow in the normal oocyte indicates the pronuclei. Scale bar = 40 μm. (C) Locations and conservation of mutations in CDC20. (D) The effects of the mutations on CDC20 and cyclin B1 protein level by Western blot in transfected CHO cells. (E) Left: Quantitation of blank, wild type (WT) and mutant CDC20 protein level in Fig. 1D. The data are shown as means and SD. **P < 0.01, ***P < 0.001, ns, not significant. Right: Quantitation of cyclin B1 protein level of overexpression the WT and mutant CDC20 in Fig. 1D. The data are shown as means and SD. *P < 0.05; ns, not significant. The experiment was performed with three independent biological replicates yielding similar results. (F) The effects of the mutations of p.Arg182* and p.Arg322Gln on CDC20 protein level by Western blot in LCLs of individual II-1 in family 3 Mutational screening of CDC20 were pursed in a large cohort of 1,250 infertile individuals with abnormalities in oocyte maturation, fertilization and early embryonic development by whole exome sequencing. Additional biallelic mutations in CDC20 were detected in another three individuals from families 3–5 (Fig. 1A). The compound heterozygous mutations in CDC20 in the affected individual in family 3 consisted of a missense mutation c.965G>A (p. Arg322Gln) and a nonsense mutation c.544C>T (p. Arg182*). The proband in family 4 carried a compound heterozygous mutation consisting of a missense mutation c.965G>A (p.Arg322Gln) and a 4 bp insertion c.813_814ins AGTG (p.Gly272Serfs*24). The proband in family 5 carried a compound heterozygous mutation consisting of a missense mutation c.965G>A (p.Arg322Gln) and a 4 bp deletion c.1176_1179del TCTG (p.Cys392*). Sanger sequencing were performed to confirm the mutations in these three families (Fig. 1A). Information about the mutations is shown in Fig. 1A and Table S2, and the positions of the mutations and their conservation in different species are shown in Fig. 1C. In family 3, oocytes were immature when retrieved. Most of immature oocytes could develop into the first polar body (PB1) oocytes after 2 hours’ in vitro culture, but showed fertilization failure or early embryonic arrest. The proband in family 4 and family 5 had phenotypes of fertilization failure or early embryonic arrest. The specific clinical information is indicated in Fig. 1B and Table S1. In transfected Chinese hamster ovary (CHO) cells, the missense mutations p.Tyr228Cys and p.Leu439Arg resulted in a reduction in CDC20 protein level, while mutations p.Arg182*, p.Gly272Serfs*24, and p.Cys392* resulted in truncated proteins (Fig. 1D and 1E). For mutation p.Arg322Gln, though there was no obvious effect on CDC20 protein level in CHO cells, the Western blot analysis of lymphoblastoid cell line (LCL) of the affected individual II in family 3 with a missense mutation c.965G>A (p. Arg322Gln) and a nonsense mutation c.544C>T (p. Arg182*) showed significantly reduced protein level (Figs. 1F and S3A). In addition, the mRNA expression of CDC20 in the LCLs of individual II-1 in family 3 and in the granulosa cells (GCs) of individual II-1 in family 4 were also reduced significantly (Fig. S3B and S3C). We also explored the effects of the mutations (c.683A>G, c. 813_814ins AGTG, c.1176_1179del TCTG, and c.1316T>G) on mRNA expression in transfected CHO cells, and the results showed that all these four mutations caused significantly reduced mRNA expression (Fig. S4). All these results indicate that mutations in CDC20 lead to unstable protein and degraded RNA per se. During the metaphase to anaphase transition, APC/C is activated through the release from CDC20 inhibition, and this leads to the breakdown of cyclin B1 (HGNC:1579) (Nasmyth and Haering, 2005). We therefore determined the effects of CDC20 mutations on cyclin B1 degradation. As shown in Fig. 1D and 1E, overexpression of wild-type CDC20 significantly decreased the endogenous protein level of cyclin B1, while most of mutations affected the degradation of cyclin B1. We next investigated the effects of the mutations on human CDC20 localization in mouse oocytes. For the three missense mutations (p.Tyr228Cys, p.Arg322Gln, p.Leu439Arg), CDC20 showed normal kinetochore localization as the wild-type. In contrast, CDC20 failed to localize to the kinetochore for the other three nonsense or frameshift mutations (p.Arg182*, p.Gly272Serfs*24, p.Cys392*) (Fig. 2A), indicating these are loss-of-function mutations. Effects of mutations on CDC20 localization and function in mouse oocytes and phenotypic rescue by CDC20 cRNA injection into oocytes from the proband of family 3 and family 4. (A) Localization of WT and mutant FLAG-tagged CDC20 in mouse oocytes. Hoechst and Crest were used to label the DNA and kinetochores, respectively. (B) The effects of the mutations on the rescue of PB1 extrusion in Cdc20 knockdown mouse oocytes with phenotype of MI arrest. The number of oocytes used are listed on top of the column. Three independent experiments were performed. ****P < 0.0001; ns, not significant. (C) One PB1 oocyte of individual II-1 in family 3 underwent ICSI without CDC20 cRNA injection was used as control. Day 0 indicates the time point at 4 h after ICSI. The black arrowhead indicates the polar body. Scale bar = 40 μm. (D) Four retrieved PB1 oocytes of individual II-1 in family 3 were injected with CDC20 cRNA and cultured for 4 h and then used for ICSI. Oocytes were monitored for 6 days after ICSI. The white arrows indicate the pronuclei. (E)Three retrieved PB1 oocytes of individual II-1 in family 4 were injected with CDC20 cRNA and cultured for 4 h and then used for ICSI. (F) Trophectoderm cells from the blastocyst embryo of individual II-I in family 3 were collected and sequencing for chromosomal copy number variation analysis Knockdown of the Cdc20 gene exclusively blocks PB1 extrusion in mouse oocytes and the PB1 extrusion can be rescued by injecting Cdc20 cRNA into the oocytes (Reis et al., 2007). To further explore the effect of mutations on CDC20 function in oocytes, we first knocked down the endogenous Cdc20 in mouse oocytes by using Cdc20 siRNA, and we observed an MI arrest phenotype that could be rescued by supplementation with human wild-type CDC20 cRNA (Fig. 2B). We then performed a rescue experiment using patient-derived mutant cRNAs in the same way. Compared with wild-type, all mutations significantly reduced the ability of CDC20 to rescue PB1 extrusion (Fig. 2B). These results indicate the overall impaired effect on CDC20 function of homozygous and compound heterozygous mutations. We then explored a potential therapeutic treatment for two patients by CDC20 cRNA injection. For the proband in family 3, compared with control, all four oocytes injected with CDC20 cRNA were successfully fertilized as indicated by the formation of two pronuclei on day 1, and two of the oocytes developed into blastocysts on day 6 (Fig. 2C and 2D). For the proband in family 4, all three oocytes injected with CDC20 cRNA were successfully fertilized on day 1, and one developed into an eight-cell stage embryo (Fig. 2E). Preimplantation genetic screening showed that one of blastocysts in family 3 had normal numbers of chromosomes and no obvious large repetition/deletion fragments (Fig. 2F). These results provide a potential treatment for these patients in the future. We found phenotypic variability among the affected individuals with CDC20 mutations. In brief, the proband in family 1 and 2 had the phenotype of oocyte maturation arrest. Although the proband in family 3 had a slight delay in oocyte maturation, the ultimate phenotype in family 3 and 4 was characterized by fertilization failure. The proband in family 5 showed early embryonic arrest. It has been reported in mice that Cdc20 has the highest expression in metaphase II (MII) oocytes compared to GV and MI oocytes as well as early embryos (Amanai et al., 2006), and this expression pattern was also observed in our qRT-PCR results in human oocytes and early embryos (Fig. S5). It is therefore likely that different amounts of CDC20 are needed at different stages of oocyte maturation, fertilization, and early embryo development. As for the mutations we identified, both family 1 and 2 had homozygous missense mutations, while families 3–5 harbored heterozygous compound mutations including one missense mutation and either a nonsense mutation or a frameshift mutation. The combinations of various types of mutations may result in different degrees of impairment of CDC20 and thus could lead to phenotypic variability. Although CDC20 plays an important role in both mitosis and meiosis (Musacchio and Hardwick, 2002; Jones, 2011), all affected individuals in the study only exhibited the phenotype of female infertility without any abnormalities in somatic tissues or organs. This might due to the different thresholds of CDC20 amount required between mitosis and meiosis (Fig. S5). In addition, previous studies showed that Cdc20 knockout mice were embryonic lethal, while Cdc20 hypomorphic mice with graded reduction of CDC20 protein level from 60%–27% were healthy and had a normal lifespan compared to wild type mice, but only female hypomorphic mice with 27% CDC20 protein level were infertile or subfertile (Jin et al., 2010; Malureanu et al., 2010). In contrast, in mitosis even profound reduction of CDC20 levels to 10% of normal still supports the onset of anaphase and the completion of mitosis (Wolthuis et al., 2008). All of these results indicate that female infertility resulting from CDC20 reduction is dosage dependent and that mitosis is more tolerant than meiosis to CDC20 reduction. In summary, we identified biallelic mutations in CDC20 responsible for variable phenotypes of female infertility characterized by abnormalities in oocyte maturation, fertilization and early embryonic development and implicated cRNA injection strategy for a potential therapeutic treatment for these patients. The online version of this article (https://doi.org/10.1007/s13238-020-00756-0) contains supplementary material, which is available to authorized users. This work was supported by the National Key Research and Development Program of China (2016YFC1000600, 2017YFC1001500 and 2018YFC1003800), the National Natural Science Foundation of China (Grant Nos. 81725006, 81822019, 81771581, 81971450 and 81971382), the project supported by Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), Project of Shanghai Municipal Science and Technology Commission (19JC1411001), the Shanghai Rising Star Program (17QA1400200), the Natural Science Foundation of Shanghai (19ZR1444500, 17ZR1401900), Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (18SG03). The Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine, Ferring Pharmaceuticals and Chinese Academy of Sciences (FIRMC200507). The capacity Building Planning Program for Shanghai Women and Children’s Health Service. The collaborative innovation center project construction for Shanghai women and children’s health. Lei W, Q S and L Z conceived and designed the research study. Y K, S X, Ling W, X S, Z Y, J S,L S, Y X, Z Y, B L, X M, J F contributed to the recruitment, characterization, and oocyte imaging of the patients, S X and B L performed the mRNA injection of patients’ oocytes. Q S performed the microinjection in mouse oocytes, B C and Q L contributed to the bioinformatics analysis. L Z performed the experiments, Jing D provided the mouse keeping room, S L and X L contributed to the establishment of LCLs. J M, Wenjing W organized the medical records. Z Z, Jie D and Weijie W analysed the data. L Z, Lei W and Q S wrote the draft of this manuscript. L J and L H helped in editing and improving the manuscript. We thank the patients and their families for participating in this study, as well as the doctors for contributing to patients’ samples collection and clinical support. Lin Zhao, Songguo Xue, Zhongyuan Yao, Juanzi Shi, Biaobang Chen, Ling Wu, Lihua Sun, Yao Xu, Zheng Yan, Bin Li, Xiaoyan Mao, Jing Fu, Zhihua Zhang, Jian Mu, Wenjing Wang, Jing Du, Shuai Liu, Jie Dong, Weijie Wang, Qiaoli Li, Lin He, Li Jin, Xiaozhen Liang, Yanping Kuang, Xiaoxi Sun, Qing Sang, and Lei Wang declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the ethical committee of the Shanghai East Hospital affiliated with Tongji University, the Ninth Hospital affiliated with Shanghai Jiao Tong University, IRB of the Medical College of Fudan University and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed. Supplementary Materials and Methods

This work provides a comprehensive review of the recent advancements in the toughening modification methods for epoxy resins. The study explores a variety of approaches, including the incorporation of liquid rubbers, core-shell rubber particles, thermoplastic resins, hyperbranched polymers, and the nanoparticle toughening method, each of which contributes to improving the mechanical properties and fracture toughness of epoxy resins. Special attention is given to the mechanisms underlying these toughening methods, such as reaction-induced phase separation, crack pinning, and energy dissipation through particle deformation. The paper also examines the synergistic effects achieved by combining different toughening agents, such as phenoxy thermoplastic rubber and core-shell rubber particles, which significantly enhance the critical fracture energy and impact strength of epoxy composites. Additionally, the challenges associated with each method, such as the potential reduction in mechanical properties and the influence of phase separation on material performance, are discussed. Through a detailed analysis of experimental studies, this paper highlights the effectiveness of various toughening strategies and suggests future research directions aimed at further optimizing epoxy resin toughening techniques for diverse industrial applications. Emerging computational modeling and machine learning applications in epoxy resin development are also systematically reviewed to highlight their potential in advancing predictive design frameworks.

Localized administration of anti-inflammatory agents benefits patients after myocardial infarction (MI) by repressing/modulating inflammatory response of the MI region and thus accelerating repair of the impaired tissues. Colchicine (Col), an ancient natural drug, has excellent anti-inflammatory effects; however, its utilization is strictly limited due to its severe systemic toxicity and narrow therapeutic window. In this study, we developed an intramyocardial delivery system of Col using an injectable, thermosensitive poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer hydrogel as the vehicle for the treatment of MI while minimizing its systemic toxicity. The aqueous PLGA-PEG-PLGA solution loaded with Col (Col@Gel) underwent a sol-gel transition at 35 °C and maintained a gel state at body temperature. Col was released from the Col@Gel in an initial burst followed by a sustained release manner for over 8 days. The in vitro cell tests showed that the Col@Gel system significantly inhibited macrophage proliferation and migration. In a mouse model of MI, a single intramyocardial administration of the Col@Gel effectively alleviated cardiac inflammation, inhibited myocardial apoptosis and fibrosis, improved cardiac function and structure, and increased mouse survival without inducing severe systemic toxicity, which was observed following intraperitoneal administration of Col solution. These results suggested that the Col@Gel system is a reliable drug delivery system for the sustained local release of Col and has great potential as an anti-inflammatory therapy for the treat of MI.

Abstract Degradability of biomaterials brings many opportunities as well as great challenges to their clinical applications. However, reports of systematic in vivo biodegradation are rather limited due to lack of adequate methodology for real‐time observations. Herein, a tri‐modal bioimaging technique is developed, enabling real time monitoring of biodegradation of synthetic polymers in vivo. The demonstrated material is a successful preclinical poly(lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(lactic acid‐co‐glycolic acid) thermosensitive hydrogel that undergoes a spontaneous sol–gel transition upon heating. A macromolecular fluorescence probe and a contrast agent of magnetic resonance imaging (MRI) are designed and synthesized. After subcutaneous injection of the hydrogel containing the two probes into mice, the degradation behaviors of the material are longitudinally and noninvasively tracked via the collaborative application of ultrasound, fluorescence, and MRI. Integrating the noninvasive imaging with the traditional anatomic observations, a three‐stage degradation mechanism of such a hydrogel is proposed for the first time. Also, the dissolved polymers and degradation products in the body are mainly eliminated via liver, gallbladder, and spleen. This work has great value for promoting the future clinical application of these kind of promising hydrogels. Meanwhile, this technological platform provides beneficial inspiration and methodology to investigate in vivo fate of biomaterials.

This study aims to investigate the effect of the stepwise marine fuel oil regulations on the concentrations of vanadium (V) and nickel (Ni) in ambient air based on a 4-y (2017-2020) online measurement in Shanghai, a coastal city in China. The annual concentration of V was reduced by 58% due to the switch from Domestic Emission Control Area (DECA) 1.0 to DECA 2.0 and further by 74% after the implementation of the International Maritime Organization (IMO) 2020 regulation, while the reduction rate for Ni was only 27% and then 18% respectively. Consistently, a reduction of 84% in V content and a negligible change in Ni content were measured in 180cst ship oil samples from 2010 to 2020. The similar increasing trend of Ni/V ratios (from <0.4 to >2.0) in both ambient measurement and heavy fuel oil samples suggests that the DECA and IMO 2020 regulations effectively reduced the ambient V. However, nickel content is still enriched in the in-use desulfurized residual oils and ship-emitted particles in coastal China. Meanwhile, the previous ratio between V and Ni cannot be used as a tracer for identifying ship-emitted particles due to its large variation in oils. Further updating of the source profile of ship traffic emissions in coastal cities is necessary in the future.

Abstract Sodium‐ion batteries (SIBs) are a promising candidate for grid‐scale energy storage, however, the sluggish ion‐diffusion kinetics brought by the large radius of Na+ seriously limits the performance of SIBs, let alone at low temperatures. Herein, a confined acid–base pair self‐assembly strategy to synthesize unusual Ti0.88Nb0.88O4−x@C for high‐performance SIBs operating at room and low temperatures is proposed. The confinement self‐assembly of the acid–base pair around the micelles and confined crystallization by the carbon layer realize the formation of ordered and stoichiometric mesoporous frameworks with opened ion channels. Thus, the mesoporous Ti0.88Nb0.88O4−x@C exhibits rapid Na+ diffusion kinetics at 25 and −40 °C, which are one order higher than that of the nonporous one. A high reversible capacity of 233 mAh g−1, excellent rate (a specific capacity of 103 mAh g−1 at 50 C), and cycling performances (<0.03% fading per cycle) can be observed at 25 °C. More importantly, even at −40 °C, the mesoporous Ti0.88Nb0.88O4–x@C can still deliver the 161 mAh g−1 capacity, a high initial Coulombic efficiency of 60% and outstanding cycling stability (99 mAh g−1 at 0.5 C after 500 cycles). It is believed this strategy opens a new avenue for constructing novel mesoporous electrode materials for low‐temperature energy storage.

Background Abnormal pronuclear formation during fertilisation and subsequent early embryonic arrest results in female infertility. In recent years, with the prevalence of assisted reproductive technology, a few genes have been identified that are involved in female infertility caused by abnormalities in oocyte development, fertilisation and embryonic development. However, the genetic factors responsible for multiple pronuclei formation during fertilisation and early embryonic arrest remain largely unknown. Objective We aim to identify genetic factors responsible for multiple pronuclei formation during fertilisation or early embryonic arrest. Methods Whole-exome sequencing was performed in a cohort of 580 patients with abnormal fertilisation and early embryonic arrest. Effects of mutations were investigated in HEK293T cells by western blotting and immunoprecipitation, as well as minigene assay. Results We identified a novel homozygous missense mutation (c.397T>G, p.C133G) and a novel homozygous donor splice-site mutation (c.546+5G>A) in the meiotic gene REC114. REC114 is involved in the formation of double strand breaks (DSBs), which initiate homologous chromosome recombination. We demonstrated that the splice-site mutation affected the normal alternative splicing of REC114, while the missense mutation reduced the protein level of REC114 in vitro and resulted in the loss of its function to protect its partner protein MEI4 from degradation. Conclusions Our study has identified mutations in REC114 responsible for human multiple pronuclei formation and early embryonic arrest, and these findings expand our knowledge of genetic factors that are responsible for normal human female meiosis and fertility.

Alzheimer's Disease (AD) is closely connected to aberrant lipid metabolism. However, how early AD-like pathology synchronously influences brain and plasma lipidome in AD mice remains unclear. The study of dynamic change of lipidome in early-stage AD mice could be of great interest for the discovery of lipid biomarkers for diagnosis and monitoring of early-stage AD. For the purpose, an untargeted lipidomic strategy was developed for the characterization of lipids (≤ 1,200 Da) perturbation occurring in plasma and brain in early-stage AD mice (2, 3 and 7 months) by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. Significant changes were detected in the levels of several lipid species including lysophospholipids, phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and Ceramides (Cers), as well as other related lipid compounds such as fatty acids (FAs), diacylglycerols (DGs) and triacylglycerols (TGs) in AD mice. In this sense, disorders of lipid metabolism appear to involve in multiple factors including overactivation of phospholipases and diacylglycerol lipases, decreased anabolism of lysophospholipids in plasma and PEs in plasma and brain, and imbalances in the levels of PCs, FAs and glycerides at different ages. We revealed the changing panels of potential lipid biomarkers with the development of early AD. The study raises the possibility of developing lipid biomarkers for diagnosis of early-stage AD.